Methylation and silencing of the Thrombospondin-1 promoter in human cancer

Qing Li, Nita Ahuja, Peter C. Burger, Jean Pierre J. Issa

Research output: Contribution to journalArticle

Abstract

Neovascularization is a common feature of many human cancers, but relatively few molecular defects have been demonstrated in genes regulating angiogenesis. Decreased expression of Thrombospondin-1 (THBS1), a P53 and Rb regulated angiogenesis inhibitor, has been observed in some human tumors, including glioblastoma multiforme (GBM). To study whether methylation-associated inactivation is involved in down-regulating THBS1 expression in cancer, we analysed the methylation status of THBS1 in several cell lines and primary tumors. Three cell lines (RKO, CEM and RAJI) were completely methylated at several CpG sites within the THBS1 5' CpG island, and had no detectable expression by RT-PCR. THBS1 expression was readily reactivated using the methylation-inhibitor 5-deoxy-azacytidine in all three lines. Furthermore, THBS1 methylation was present in 33% (14/42) of primary GBMs. Thus, de novo methylation may serve as a potential way to inactivate THBS1 expression in human neoplasms.

Original languageEnglish (US)
Pages (from-to)3284-3289
Number of pages6
JournalOncogene
Volume18
Issue number21
DOIs
StatePublished - May 27 1999

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Keywords

  • Angiogenesis
  • DNA methylation
  • Glioblastoma multiforme
  • Thrombospondin-1 (THBS1)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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